{"orpha":1933,"name":"Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Booth-Haworth-Dilling syndrome","Mitochondrial encephalomyopathy-aminoacidopathy syndrome","mtDNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria"],"definition":"A rare mitochondrial DNA depletion syndrome characterized by neonatal or infantile onset of global developmental delay, hypotonia, failure to thrive, progressive neurologic decline, sensorineural deafness, and movement disorder. Seizures, external ophthalmoplegia, polyneuropathy, cardiomyopathy, and renal tubular dysfunction have also been reported. Brain imaging may show T2-weighted hyperintensities in the basal ganglia, and laboratory examination may reveal lactic acidosis and mild methylmalonic aciduria.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-1933/","orphanet_url":"https://www.orpha.net/en/disease/detail/1933","names":{"fr":{"name":"Syndrome de déplétion de l'ADN mitochondrial forme encéphalomyopathique avec acidurie méthylmalonique","synonyms":["Syndrome d'encéphalomyopathie mitochondriale-aminoacidopathie","Syndrome de Booth-Haworth-Dilling","Syndrome de déplétion de l'ADNmt, forme encéphalomyopathique avec acidurie méthylmalonique"],"definition":"Syndrome rare de déplétion de l'ADN mitochondrial caractérisé par l'apparition néonatale ou infantile d'un retard global de développement, d'une hypotonie, d'un retard de croissance, d'un déclin neurologique progressif, d'une surdité neurosensorielle et de mouvements anormaux. Des convulsions, une ophtalmoplégie externe, une polyneuropathie, une cardiomyopathie et un dysfonctionnement des tubules rénaux ont également été rapportés. L'imagerie cérébrale peut mettre en évidence des hyperintensifications des noyaux gris centraux sur la séquence pondérée en T2, et l'analyse biologique peut révéler une acidose lactique et une légère acidémie méthylmalonique."},"de":{"name":"Mitochondriales DNA-Depletionssyndrom, enzephalomyopathische Form mit Methylmalonazidurie","definition":"Ein seltenes mitochondriales DNA-Depletionssyndrom, das durch eine globale Entwicklungsverzögerung, Hypotonie, Gedeihstörung, fortschreitende neurologische Verschlechterung, sensorineurale Taubheit und Bewegungsstörungen gekennzeichnet ist, die im Neugeborenen- oder Säuglingsalter auftreten. Es wurde auch über Krampfanfälle, externe Ophthalmoplegie, Polyneuropathie, Kardiomyopathie und renale tubuläre Dysfunktion berichtet. Die Bildgebung des Gehirns kann T2-gewichtete Hyperintensitäten in den Basalganglien zeigen, und die Laboruntersuchung kann eine Laktatazidose und eine leichte Methylmalonsäureurie ergeben."},"es":{"name":"Síndrome de depleción del ADN mitocondrial, forma encefalomiopática con aciduria metilmalónica","synonyms":["Síndrome de Booth-Haworth-Dilling","Síndrome de depleción del ADNmt, forma encefalomiopática con aciduria metilmalónica","Síndrome de encefalomiopatía mitocondrial-aminoacidopatía"],"definition":"Es un síndrome de depleción del ADN mitocondrial caracterizado por la aparición neonatal o en la lactancia de un retraso global del desarrollo, hipotonía, fallo de medro, afectación neurológica progresiva, sordera neurosensorial y trastornos del movimiento. También se ha descrito crisis, oftalmoplejía externa, polineuropatía, cardiomiopatía y disfunción tubular renal. La neuroimagen puede mostrar hiperintensidades ponderadas en T2 en los ganglios basales, y las pruebas bioquímicas pueden revelar acidosis láctica y leve aciduria metilmalónica."},"it":{"name":"Sindrome da deplezione del DNA mitocondriale, forma encefalomiopatica con aciduria metilmalonica","synonyms":["Encefalomiopatia mitocondriale - aminoacidopatia","Sindrome da deplezione del mtDNA, forma encefalomiopatica con aciduria metilmalonica","Sindrome di Booth-Haworth-Dilling"],"definition":"Si tratta di una malattia rara da deplezione del DNA mitocondriale, che esordisce in epoca neonatale o nell'infanzia con ritardo dello sviluppo globale, ipotonia, ritardo della crescita, declino neurologico progressivo, sordità neurosensoriale e anomalie del movimento. I pazienti possono presentare anche crisi epilettiche, oftalmoplegia esterna, polineuropatia, cardiomiopatia e disfunzione tubulare renale. Le neuroimmagini evidenziano iperintensità nelle sequenze T2-pesate nei gangli basali, mentre gli esami di laboratorio evidenziano acidosi lattica e aciduria metilmalonica lieve."},"nl":{"name":"Mitochondriaal DNA-depletiesyndroom, encefalomyopathische vorm met methylmalonacidurie","synonyms":["Mitochondriaal DNA-depletiesyndroom, encefalomyopathische vorm met methylmalonacidemie","Mitochondriaal DNA-depletiesyndroom, encefalomyopathische vorm met methylmalonzuuracidurie","Mitochondriale encefalomyopathie - aminoacidopathie-syndroom","Syndroom van Booth-Haworth-Dilling","mtDNA-depletiesyndroom, encefalomyopathische vorm met methylmalonacidemie","mtDNA-depletiesyndroom, encefalomyopathische vorm met methylmalonacidurie","mtDNA-depletiesyndroom, encefalomyopathische vorm met methylmalonzuuracidurie"],"definition":"Een zeldzaam mitochondriaal DNA-depletiesyndroom, gekarakteriseerd door neonatale of infantiele aanvang van algehele ontwikkelingsachterstand, hypotonie, niet-gedijen, progressieve neurologische aftakeling, sensorineurale doofheid, en bewegingsstoornis. Insulten, externe oftalmoplegie, polyneuropathie, cardiomyopathie, en disfunctie van niertubuli werden ook reeds gerapporteerd. Beeldvorming van hersenen toont mogelijk T2-gewogen hyperintensiteiten in basale ganglia, en laboratoriumonderzoek kan lactaatacidose en milde methylmalonacidurie aantonen."},"pt":{"name":"Síndrome de depleção do ADN mitocondrial, forma encefalomiopática com aciduria metilmalónica","synonyms":["Encefalomiopatia aminoacidopatia mitocondrial","Síndrome Booth-Haworth-Dilling","Síndrome de depleção do ADNmt, forma encéfalomiopática com acidúria metilmalónica"]},"pl":{"name":"Zespół deplecji mitochondrialnego DNA, forma z encefalomiopatią i kwasicą metylomalonową","synonyms":["Mitochondrialna encefalomiopatia - aminoacidopatia","Zespół Bootha, Hawortha i Dillinga","Zespół deplecji mtDNA, forma z encefalomiopatią i kwasicą metylomalonową"]},"cs":{"name":"Syndrom deplece mitochondriální DNA, encefalomyopatická forma s methylmalonovou acidurií","synonyms":["Syndrom zahrnující mitochondriální encefalomyopatii a aminoacidopatii","Syndrom mtDNA deplece, encefalomyopatická forma s methylmalonovou acidurií","Boothův-Haworthův-Dillingův syndrom","Booth-Haworth-Dillingův syndrom"]},"uk":{"name":"Синдром виснаження мітохондріальної ДНК, енцефаломіопатична форма з метилмалоновою ацидурією","synonyms":["Синдром Бута-Хауорта-Діллінга","Синдром мітохондріальної енцефаломіопатії-аміноацидопатії","Синдром виснаження мтДНК, енцефаломіопатична форма з метилмалоновою ацидурією"],"definition":"A rare mitochondrial DNA depletion syndrome characterized by neonatal or infantile onset of global developmental delay, hypotonia, failure to thrive, progressive neurologic decline, sensorineural deafness, and movement disorder. Seizures, external ophthalmoplegia, polyneuropathy, cardiomyopathy, and renal tubular dysfunction have also been reported. Brain imaging may show T2-weighted hyperintensities in the basal ganglia, and laboratory examination may reveal lactic acidosis and mild methylmalonic aciduria."},"zh":{"name":"线粒体DNA耗竭综合征，脑肌病伴甲基丙二酸尿症型","synonyms":["线粒体脑肌病-氨基酸代谢病综合征"]},"tr":{"name":"Mitokondriyal DNA deplesyon sendromu, metilmalonik asidüri ile ensefalomyopatik form","synonyms":["mtDNA tükenme sendromu, metilmalonik asidüri ile seyreden ensefalomiyopatik form","Booth-Haworth-Dilling sendromu","Mitokondriyal ensefalomiyopati-aminoasidopati sendromu"]}},"xrefs":[{"source":"OMIM","code":"612073","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.20","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1143431651"},{"source":"MONDO","code":"0012791","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2749864","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3681","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":254803,"name":"Mitochondrial DNA depletion syndrome, encephalomyopathic form","classifications":[150,156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"SUCLA2","name":"succinate-CoA ligase ADP-forming subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"17287286[PMID]_20301762[PMID]","hgnc":"11448","ensembl":"ENSG00000136143","omim":"603921","loci":["13q14.2"]}],"genes_via_subtypes":[],"inheritance":["Mitochondrial inheritance"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"2738799[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_2738799[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0000512","label":"Abnormal electroretinogram","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000649","label":"Abnormality of visual evoked potentials","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003355","label":"Aminoaciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004326","label":"Cachexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002514","label":"Cerebral calcification","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000762","label":"Decreased nerve conduction velocity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002230","label":"Generalized hirsutism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0006887","label":"Intellectual disability, progressive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012120","label":"Methylmalonic aciduria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Very frequent (99-80%)","criteria":null}]}}